Design and prototype of TOMO: an app for improving drug resistant TB treatment adherence

Background: Drug resistance and multi drugs tuberculosis (DR/MDR-TB) are associated with patients’ low adherence to undergoing complex treatment. Driven by the increasing use and penetration of a smartphone and the End of TB Strategy that seeks for digital health solution, Center for Tropical Medicine Universitas Gadjah Mada has developed TOMO, an Android-based app for improving medication adherence in MDR-TB. Objective: This paper aims to present the sequential steps to develop the app, its general architecture, and its functionalities. Methods: It is a design thinking process involving two MDR-TB referral centers, district health offices, primary health centers, and MDR-TB patients in Central Java and Yogyakarta, Indonesia. We adopted the Principles for Digital Development to develop and design the app. MDR-TB treatment guideline from the Indonesian Ministry of Health was used to develop functionalities of the app for improving adherence. Results: TOMO app could be used by patients, primary health centers, clinical teams, and case managers. The app prototype features include adverse event records and reports, medication-taking reminders, and communication between the patient and the TB-MDR case manager. We have successfully tested the functionalities based on four use cases: patients with high adherence, patients with low adherence, patients with adverse events, and patients following treatment in the primary health center without any visit to the MDR-TB center. Conclusion: TOMO app has contributed to the limited body of literature on improving TB-MDR adherence with digital health intervention, especially using a health app. The app has been tested using four scenarios. We will follow up with usability testing before implementing the app in a real setting.


Introduction
Multi-drug resistant tuberculosis (MDR-TB) is associated with high treatment failure due to low adherence of patients inù ndergoing the complex treatment process. 1 The prolonged duration of treatment, the huge opportunity costs incurred by daily visits to health facilities, and the wide range of adverse drug events have been associated with high default rates of MDR-TB patients. 1[4] In Indonesia, the country with the fourth largest tuberculosis (TB) burden, MDR-TB cases are alarming.It is estimated that there are 32,000 cases of MDR-TB of which only 8% were detected in the TB program.The performance of MDR-TB case management urgently needs to be improved.In 2016, about 29% of cases died within the first six months after diagnosis, and 19% did not continue treatment.Therefore, a patient-centered care approach is necessary to support MDR-TB patients during long treatment to ensure medication adherence, oversee potential side effects, and offer psychosocial support.Adherence to the long course of TB-MDR treatment is a complex endeavor involving multiple factors that influence patients' motivation and behavior in treatment-taking. 1,5,62][13][14] In developing countries, m-health is mainly used for providing disease information, reminders for care, and telemedicine.However, few m-Health applications exist for TB.Iribarren et al. (2016) found only two apps, and none were related to TB treatment self-management or patient-provider interaction. 15gital health technologies have been considered a potential tool to improve medication adherence in tuberculosis. 9,14hrough mobile health innovations, patients will be empowered to easily request consultation and advice regarding treatment regimen, scheduling, and side effects.A recent study exploring patients and medical staffs in six countries reported a high enthusiasm for e-health innovation to support TB programmes, including apps 16 and video observing treatment apps. 17gital health intervention has been recommended by WHO to strengthen health systems in at least nine use cases. 18igital health intervention is projected to contribute to substantial cost saving and improvement of TB programs. 13,19A comprehensive review of the potential for digital health in TB programmes has been published.However, there are still only a few studies that attempt to explain the role of digital health innovation in improving medication adherence.
Along with the increasing ownership of cellular phones, especially smartphones, health intervention through applications is no longer just a reminder or reciprocal communication.Health apps can also act as an integrated application that includes various functions developed for specific purposes.In this context, we intend to report on the design and technical overview of apps specifically designed to help manage the MDR-TB program.This paper aims to: 1. Describe sequential steps to develop apps involving multiple stakeholders in the MDR-TB program 2. Draw technical architecture and interoperability of the app with the existing MDR-TB information system 3. Test features and functionalities of the app based on scenarios in the real setting.

Methods
This study was a collaborative work by the Center for Tropical Medicine Universitas Gadjah Mada, Dr. Sardjito hospital in Yogyakarta province, Dr. Moewardi hospital in Central Java province, and Computer Science department of Universitas Gadjah Mada.Following subsequent steps in design thinking, all collaborators teamed up to develop the best health app solution to improve MDR-TB treatment adherence.
Participants in this study were patients with MDR-TB in Dr. Moewardi hospital, healthcare professionals (pulmonologists from Dr. Sardjito and Dr. Moewardi hospital, MDR-TB case manager at hospital and primary health care level), and district health department officers.Researchers from the Center for Tropical Medicine Universitas Gadjah Mada were the principal investigators in this study and translating user needs from clinical setting perspectives into health app workflow and design.

Study design
Five steps of design thinking were adopted in this study; empathize, define, ideate, prototype, and test. 20Design thinking is an analytic and creative approach in solving problems or fulfilling user needs in the app development context. 21,22erspectives from multiple stakeholders or users that will use the health app were the most important data in the app development processes.The details of each step and type of data collected are depicted in Table 1.We conducted meetings with two MDR-TB referral hospitals; Dr. Sardjito hospital in Yogyakarta province and Dr. Moewardi hospital in Central Java province.The first meeting with Dr. Sardjito hospital icluded the empathize and define processes to collect and summarize any stories and problems that providers had in monitoring MDR-TB treatment.In addition, this study also collected information from MDR-TB patients to ensure the app covered all user needs.After problems were defined, the ideate process was started by creating a list of possible solutions and the workflow of TB application features.The prototype process based on the chosen solution was conducted iteratively.Dr. Moewardi hospital was used as the primary setting to improve the workflow of the TB app.Two workshops to introduce the app for case managers, physicians, and 13 PHC in Dr. Moewardi's area were conducted in the test process.
Prior to the workshop, a simulation mimicking use cases in a real setting was conducted by researchers.
In 2017-2018, Dr. Moewardi hospitals provided treatment to 207 patients.MDR-TB clinic in this hospital is supported by one pulmonologist, one dedicated case manager, five other supporting staff.This hospital utilized TB-Manager, a webbased application from the Ministry of Health, to register, monitor, and report the MDR-TB program.Later, this program was changed with a new electronic system called SITB (Sistem Informasi TB).For internal purposes, the hospital also implemented a hospital information system for billing and recording all patients' transactions, including MDR-TB.

Ethical considerations
This study was started in September 2019.The study protocol and procedure were approved by the Ethical Committee of the Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta (No: KE/FK/0990/EC/2019 and KE/FK/1285/EC/2020).

Results
A total of four workshops and seven other activities, including observation, survey, and simulation, were conducted in this study.

Insight from the empathize and define steps
-The MDR-TB treatment monitoring using the current system was not able to track patient treatment adherence daily.Furthermore, the system was only focused on collecting patients baseline data and drug regimens.
-Primary health care performance in supervising dai drug consumption of MDR-TB patients was not monitored.Primary health care in MDR-TB treatment is vital since patients need to visit it daily to take the drugs and report any adverse events.
-Communication activities related to adverse events of MDR-TB drugs were not well organized and documented.Patients could directly consult the pulmonologist, or sometimes they could ask the case manager or primary health care first.During the consultation, the information was not recorded and could cause problems for further patient care related to the adverse events.
-Adverse drug effects were issues that influenced patient adherence to MDR-TB treatment.In addition, the patients also needed social support and opportinuies to share amongst patients with MDR-TB to improve treatment adherence.
-The findings from the patient's survey were that most patients owned an Android smartphone (69.23%), and that around 80% of respondents used internet browsers and social media apps (i.e., Whatsapp).
The solution identified from the ideation step -In workshop 2, users, researchers, and the app development team decided on solutions that would become the app's main functionalities.The first function was reporting MDR-TB drug consumption for patients and crosschecking the patients' drug consumption by healthcare workers in the hospital or primary health care.Second, a drug adverse event reporting function could be accessed by pulmonologists, case managers, and primary healthcare workers.Third, a real-time dashboard to monitor the treatment progress of TB-MDR patients.
-In order to be interoperable with the national TB information system, the research team has discussed with the TB program manager and the technical team to develop an Application Programming Interface (API), so that data from the two systems can be exchanged securely without user intervention.
-A MDR-TB patient forum within the app could help patients give social support to each other during treatment.
Post-treatment patients could also share their experiences to help other patients who are still undergoing the treatment process.
In the ideation step, some vital app features were chosen for initial prototype development.The cross-checking drug consumption, drug adverse event report and consultation, and monitoring dashboard were chosen for the initial phase.
Other important features will be developed later after the prototype's main features are implemented in the real setting.

Prototype and test step
The User Interface (UI) and User Experience (UX) were developed to depict the initial app workflow and design.After several tests and revisions by researchers and users (pulmonologists and the case manager), the technical architecture and workflow of the app were established.

The technical architecture of TOMO
The first application is for TB-MDR patients (TOMO).The second application is dedicated only to providers, including Primary Health Centers, the case manager, and the treating physician (TOMO CM).The first two applications are targeted as mobile-based applications.Before publication of this paper, we will have developed the Android application to be available on PlayStore.The third application is a web-based application that will be used as a dashboard by the government to see the usage overview of the application.The web-based application is also used as an admin tool for managing user and master data.These three applications work together to achieve the primary goal.Figure 1 shows the use diagram that describes the functionality of each user within the system.The current prototype of the TOMO application was developed in an Android environment using Kotlin programming language.Furthermore, the TOMO website was developed using PHP 7 programming language.MySQL 5.6 was used as the database management system, while Django Python (Django, RRID:SCR_012855) was used to develop the API (application programming interface) in PHP language for the application and website.
The Android applications are available on the Play store, and they can be used using Android with minimal version Kitkat (4.4).The memory needed for the TOMO app was 5.3 MB memory, and for the TOMO CM was 5.8 MB memory.

Workflow of TOMO
The sequential workflow of the prototype (Figure 2) shows the process from patient baseline data input, drug consumption monitoring process, adverse event consultation, and the in-person visit schedule feature.Each user type has a different feature in the app.The patient will be responsible for reporting drug consumption and adverse events and for viewing any scheduled visits.The case manager is responsible for inputting patient data and drug regimens, validating drug consumption, responding to patient adverse events, and creating a schedule for physician visits.The primary health center will be mostly responsible for drug consumption validation and reporting patient adverse events.The physician (Pulmonologist) is responsible for evaluating treatment progress and responses to adverse events.The interoperability of the prototype with the existing MDR-TB app was included in the workflow.The patient baseline data will be directly retrieved from the existing app using the API provided by the existing MDR-TB app.The iterative processes of the test were conducted to ensure the performance and feature suitability of the prototype.The app developer conducted alpha and beta testing for bug detection.The simulation by researchers showed that the app functionalities performed well in four different use cases: patients with high adherence, patients with low adherence, patients with adverse events, and patients following treatment in the primary health center without any visit to the MDR-TB center.Two workshops for prototype introduction were conducted by inviting all users.Through the process, the prototype workflow and interface were finalized, and prototype performance was evaluated.The final prototype interface is presented in Figure 3.

Discussion
This work represents the preliminary design of an app to support the MDR-TB program.The design thinking method in the development process was able to fulfill all user's needs.In regard to the nine principles of digital development, 23 this app development process is inline and covered all aspects of the principles (Table 2).USAID developed the principle to avoid a failure in the technology-supported program for development. 23The elaboration of the principle and design thinking method allows the MDR-TB app to be more acceptable and sustainable to improve MDR-TB treatment adherence.
Successful experiences from other countries in terms of tuberculosis-related apps were previously reported.In Brazil this consisted of a dedicated Tuberculosis information system within the notifiable disease surveillance system. 24In Peru, a web-based laboratory information system for tuberculosis was reported in improving communication delay in tuberculosis management. 25,26This work proposes a novel innovation of tuberculosis monitoring by adopting a crosschecking method of drug consumption.Through this method, patient adherence to the treatment and healthcare provider performance as the drug consumption observer could be monitored and evaluated in a real-time fashion.The adverse event consultation session data between patient and healthcare provider were collected in the system and could be used for patient treatment planning in the future.
The study in Brazil proposes web-semantic approach for solving interoperability issues between multiple systems. 27n Indonesia, an initiative has been conducted between TB information systems and hospital information systems.However, a systematic review of the literature revealed that there is a lack of evidence-based incentives for researchers to share data. 28In this regard, an integrated approach has been proposed by Fraser et al. to improve TB information system.This includes open data standards and interoperability, integration with mHealth applications, and ability to function in resource-poor environments. 29allenges of app for TB Mobile phones are the fastest adopted modern technology in developing countries, as has already happened in developed countries.The abilities and features of mobile phones are promising tools in improving community health and health literacy.However, despite the high incidence of mobile phone ownership in the population, the ownership among patients with TB itself is still low.One third of patients with TB in the United States do not have smartphone. 30The situation is similar for patients with hypertension. 31This phenomenon is no different in Indonesia -among poor families one mobile phone is usually used by more than one family member.In addition, as in other developing countries, the ownership of a mobile phone is sometimes not concurrent with the ability to get internet subscription. 32It is thus important for the government to ensure affordable internet access to all communities.
Another challenge is lack of literacy among communities.Many patients with TB come from poor families with low levels of education. 32As mentioned by many studies, lack of literacy is related to poverty and low educational attainment.Furthermore this situation usually leads to inadequate health literacy, which can inhibit the patient's desire to use novel tools like mobile applications to improve their health.It is important to understand how this particular population interacts with their mobile phone to ensure that the mobile health applications are developed according to these particualr characteristics, so that they are easy to learn and use.
TOMO as a mobile application has a high potential to help patients with MDR-TB in Indonesia.It has been explained in previous studies that patients have lower adherence to completion of treatment when they have had negative treatment experiences. 33These include substantial travel time to get access to care, missed earning time because they have to spend a lot of time at the healthcare facilities, and other expenses by the patients and family who accompanied patient to the facilities.TOMO is developed to be the solution to these difficult situations by functioning as a communication platform which can connect patients directly with their case managers and attending physicians.

Future directions
We plan to undergo several iterations of evaluation, examining both the usability and content of the app before initiating the trial in a real setting.However, a few improvements are needed based on the real use cases, including modifications of the algorithm.In the near future, data exchange between TOMO with SITB (Sistem Informasi TB) from the Ministry of Health will be exercised.After the implementation of TOMO in Dr. Moewardi Hospital, we will conduct workshops to develop a sustainability plan and initiate scaling up.
Our study has several limitations.Firstly, this evaluation of the use cases was performed in a laboratory setting by the research team members, aiming to validate the functionalities and the system workflow.Secondly, the export/import functionalities were applied based on the former electronic system, namely eTB Manager.Currently, the Ministry of Health has piloted a new electronic TB information system.This new platform offers API functionality offering electronic data exchange of certain variables into our application.We expect interoperability between our prototype with the new system before testing the application in the real setting.

Conclusion
This report depicts TOMO's design, technical architecture, and functionalities, an app for improving medication adherence in TB-MDR treatment.This app is a mobile-based platform aimed to improve communication between TB-MDR providers and patients.It contributes to the limited body of literature on improving TB-MDR adherence with digital health interventions, especially using health apps.The prototype features include the adverse event record and report system, reminders for drug taking, and a platform for communication between patients and TB-MDR case managers.The prototype will later undergo several iterations of evaluation for usability and content.Future work will involve developing this into a fully functioning app before initiating the trial in a real setting.
Background: 'multi drugs tuberculosis' to be changed as 'multi drug resistance tuberculosis' ○ TB-MDR to be changed as MDR-TB

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The terms used are m-Health, mobile health, e-TB manger, mHealth is these are same, or what is context authors describing these terms.If these are same then the same terminology to be used throughout the text.Successful experiences from other countries in terms of tuberculosis-related apps were previously reported.
Page-9 last Para: line 2 Thank you for the opportunity to review this manuscript.I have noted a few areas that require clarification.Methods How many collaborators were involved.Its wonderful to be specific about the exact number of collaborators that were part of this phase.This should be revised in the entire manuscript so that specificity and clarity and ensured.
There is a need to ensure consistency in wording, in some sections, you mention meetings while in others you mention workshops, these should be revised.Ideally it would be great to mention the composition of these meetings, how many members made up each of these meetings, how were they selected, what was the eligibility criteria, this needs to be clear and how was data from these meetings obtained, was it through recordings and later transcribed verbatim.
Health apps, deal with a huge amount of sensitive health data, how is the security of this app ensured given that unintended disclosure of health status has been cited in some literature.
Is this app available free of charge or it requires participants to pay a certain fee additionally, does it rely on the internet to function, or it has an offline version?
Provide the section of strengths and limitations of this study.

Is the work clearly and accurately presented and does it cite the current literature? Yes
Is the study design appropriate and is the work technically sound?Yes

Are sufficient details of methods and analysis provided to allow replication by others? Yes
If applicable, is the statistical analysis and its interpretation appropriate?

Not applicable
Are all the source data underlying the results available to ensure full reproducibility?Partly lot of time at the healthcare facilities, and other expenses by the patients and family who accompanied patient to the facilities.TOMO is developed to be the solution to these difficult situations by functioning as a communication platform which can connect patients directly with their case managers and attending physicians."This sentences seems to imply that if they use the app they don't need to go to the health facility daily, that the self-reported self administration of treatment (SAT) relieves them of this obligation.Is that correct?Is this a replacement for DOT?That is inferred but not explicitly stated.If it is not a form of SAT, then how exactly does TOMO solve the substantial travel time and missed earning time issue?It would be good to have a figure or a mapping of what the main reasons for forsaking treatment are (from the patient survey) and how the app's features specifically corresponds to these.

2.
There seems to be a disconnect at times between what is expressed as a need and what is provided as a service.From the survey, MDR patients report needing social support.The notion that an unmoderated chat group of MDR-patients would provide support and increase adherence is interesting, but I am unaware of the evidence to support this claim.Consider to offer some evidence to motivate the decision to have an unmoderated chat at the support intervention .Unmoderated chat groups can be used in many ways by their users.It would be good to know if the group is anonymous or not.Anonymous chat groups of vulnerable groups have not had a great track record.For example, peer-support apps for opioid disorder often contain misinformation, trolling, and harassment.How will you ensure that people with TB are not harmed in the group chat? 3.
The authors point out that there is a lot of enthusiasm for digital health for TB adherence.However, it would be good to point out that the results of digital health trials for modifying behavior of people with TB have been mixed.Qualitative work suggests that patients value the human element in their care and are not necessarily keen to interact with robots, electronic pillboxes, SMS messages.

Comment regarding the App development (not the manuscript)
The TOMO app seems to have been co-designed with pulmonologists and primary care workers.The MDR patients are surveyed at the beginning, and they are involved in testing the prototype, but the middle part of the actual design of the app features does not include them.Digital health for end users with TB that is not co-designed by people with TB can lead to them feeling even further alienated from society.It appears that health care workers are the main beneficiaries of this system as currently designed. 1.

Areas that are not yet clear to this reader:
Access to smart phones is lower among women and poorer persons.The provision of support and other benefits via smart phones and the requirement of having a bank account disadvantages women, those under 18, and the poor.Lack of electricity, internet connectivity; and low technology literacy are also more common among the poor.How can the app be modified to contribute to equity?How do the 31% without a smart phone differ from those with a smart phone? 1.
While reporting adverse events is important for the program, it is less clear how this is useful for the patient, unless there is a change in regimen or offer of symptom management.Does the app measure whether and how long it takes for there to be a clinical response?Are the reminders to respond also pinging the HCWs?Or just the patients?Reviewer Expertise: TB I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.
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Figure 3 .
Figure 3.The user interface of TOMO.

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Need to provide references for: Page-3 Para 5: line A comprehensive review of the potential for digital health in TB programmes has been published.Page-9 Para 1: line 1 ○ ○

2 .
Is the work clearly and accurately presented and does it cite the current literature?PartlyIs the study design appropriate and is the work technically sound?PartlyAre sufficient details of methods and analysis provided to allow replication by others?PartlyIf applicable, is the statistical analysis and its interpretation appropriate?Not applicableAre all the source data underlying the results available to ensure full reproducibility?No source data requiredAre the conclusions drawn adequately supported by the results?YesCompeting Interests: No competing interests were disclosed.

Table 2 .
Principles of digital development and TOMO development process.

the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Not applicable Are all the source data underlying the results available to ensure full reproducibility? No source data required Are the conclusions drawn adequately supported by the results? No Competing Interests:
Conclusion to changed; it seems to be developed the app, it needs to checked under the field condition.Overall it is a good work needs revision considering the above comments.No competing interests were disclosed.

have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Wilson Tumuhimbise
Mbarara University of Science and Technology, Mbarara, Western Region, Uganda